In pulmonary diseases, such as emphysema, adequate delivery of O2 to tissue is impaired. If pharmacological or environmental means can be employed to lower tissue O2 requirements, this could be useful treatment in such diseases and in survival during crises. In heat-acclimated mammals physiological changes occur which could serve as a model in the quest for treatment of such diseases. The resting metabolic rate of heat-acclimated (HA) rhesus (Macaca mulatta) is much lower than that of controls at any temperature of measurement between 0 and 40 degrees centigrade; in cold-acclimated (CA) rhesus it is higher. The proposed research is to seek a biochemical explanation for these metabolic differences. With better understanding it may be possible to mimic such metabolic modifications pharmacologically. Monkeys will be used instead of rodents because of closer phylogenetic relationship to man and because past research indicates that primates differ from rodents in biochemical responses in temperature acclimation. In CA animals competition among body tissues for available O2 increase; in HA animals this competition decreases. To detect which tissues are most activated metabolically in CA animals (and thus probably most depressed in HA animals) direct thermister recordings will be taken from various organs before and during norepinephrine (NE) administration. Further evidence of specific tissue NE-activated metabolism will be sought using B- adrenergic blocking agents. Measurements will also be made on isolated whole cells using ouabain and NE to test induced membrane permeability and allow estimation of the portion of O2 comsumption allocated to support the Na ion - K ion pump. Both cytoplasmic and mitochondrial enzyme systems will be studied further, and we will study extramitochondrial systems capable of influencing O2 requirements by affecting the intracellular levels of ADP and cyclic AMP. Assays of plasma membrane Na ion - K ion ATPase, levels of ADP, AMP, and certain possible rate limiting intracellular metabolites will be made in samples of brown fat, skeletal muscle, liver and kidney. Other justification for these studies springs from the fact that people who work outdoors cannot escape prolonged exposure to heat and to cold, and little is known concerning what changes in tissue biochemistry take place in primates.